High-Frequency Oscillation for ARDS Liaudet, Lucas; McDermid, Robert C; Csányi-Fritz, Yvonne I ...
The New England journal of medicine,
06/2013, Letnik:
368, Številka:
23
Journal Article
Recenzirano
Odprti dostop
To the Editor:
In their article on the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) study, Ferguson et al. (Feb. 28 issue)
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report increased mortality in patients ...with the acute respiratory distress syndrome (ARDS) who underwent high-frequency oscillatory ventilation (HFOV), probably because of elevated mean airway pressures. High levels of airway pressure may reduce venous return by elevating right atrial pressure, increasing venous resistance, and creating vascular waterfall conditions in the vena cava.
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,
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High levels of airway pressure may also increase pulmonary vascular resistance and right ventricular afterload through passive compression of alveolar vessels.
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During HFOV, the . . .
CORRESPONDENCE Kacmarek, Robert M.; Slutsky, Arthur S.
American journal of respiratory and critical care medicine,
02/2007, Letnik:
175, Številka:
3
Journal Article
Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity ...is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans.
Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. They were harvested at 14 different time points (from 1 day to 1 year after transplantation) and assessed histologically.
The fibrous airway obliteration developed only in allografts showing a triphasic time course: an initial ischemic phase (observed in both isografts and allografts) was followed by a marked lymphocytic infiltrative phase with complete epithelial loss (observed only in allografts, P<0.01), and finally by an obliterative phase with fibrous obliteration of the allograft airway lumen (P<0.01).
This animal model shows a distinct and reproducible triphasic time course in the development of obliterative airway lesions in allografts. It confirms that the mechanism leading to airway obliteration is immune mediated as only allografts showed this lesion and that lymphocytic infiltration is a precursor of the lesion in this model. The insights into the different phases demonstrated may lead to novel approaches regarding the type and timing of therapeutic interventions.
By early October, 2009, there had been more than 340 000 reported cases of H1N1 infection in 191 countries, with more than 4100 deaths.1 WHO initially projected that up to 2 billion people could ...become infected with the virus over the next 2 years.2 Although vaccination programmes and other factors should reduce this number, plausible estimates of the number of infected individuals who might benefit from admission to intensive care range from 200 000 to 10 million. Beyond antiviral agents, anecdotal reports and data from animal studies suggest that illness severity can be attenuated by readily available agents, such as corticosteroids and statins, that can modulate the host's inflammatory response.9 None of these drugs has been adequately studied for efficacy.
Rationale
Ventilator induced lung injury (VILI) significantly contributes to the mortality in patients with acute respiratory distress syndrome.
Objectives
To determine the role of vagus nerve ...signaling in VILI.
Methods
To determine whether vagus signaling plays a role in VILI we first demonstrated that disruption of the CAP reflex by bilateral vagotomy results in worsening lung injury in a mouse model of high‐volume‐induced lung injury. In a clinically relevant model of injurious mechanical ventilation following lung injury induced by hemorrhagic shock/resuscitation we then tested the hypothesis that electrical and pharmacological stimulation of the vagus nerve can attenuate lung injury in rats.
Results
Vagotomy exacerbates lung injury from high volume ventilation in mice as demonstrated by increased wet‐to‐dry ratio, infiltration of neutrophils in bronchoalveolar lavage fluid and lung tissues, and increased tissue levels of interleukin‐6. Vagotomy exacerbated while vagus stimulation attenuates lung injury in rats after ischemia reperfusion injury ventilated with either high or low volume strategies. Treatment of both mice and rats with the vagus mimetic drug, semapimod, resulted in decreased lung injury. Vagotomy also increased pulmonary apoptosis whilst vagus stimulation attenuated VILI‐induced apoptosis. In‐vitro studies suggest that vagus‐dependent effects on inflammation and apoptosis are mediated via the alpha 7 subunit of the acetylcholine nicotinic receptor effect on cyclic stretch‐dependent singling pathways c‐jun N‐terminal kinase (JNK) and Fas (TNF receptor superfamily, member 6).
Conclusion
Stimulation of the cholinergic anti‐inflammatory reflex may represent a promising alternative for the treatment of VILI.
Enlarging and Protecting an Aerated Lung Ranieri, V. Marco; Gattinoni, Luciano; Slutsky, Arthur S.
American journal of respiratory and critical care medicine,
02/2008, Letnik:
177, Številka:
4
Journal Article
Polymorphonuclear leukocytes (PMNs) play an important role during inflammation in cardiovascular diseases. Human neutrophil peptides (HNPs) are released from PMN granules upon activation and are ...conventionally involved in microbial killing. Recent studies suggested that HNPs may be involved in the pathogenesis of vascular abnormality by modulating inflammatory responses and vascular tone. Since HNPs directly interact with endothelium upon release from PMNs in the circulation, we tested the hypothesis that the stimulation with HNPs of endothelial cells modulates the expression of vasoactive by-products through altering cyclooxygenase (COX) activity. When human umbilical vein endothelial cells were stimulated with purified HNPs, we observed a time- and dose-dependent increase in the expression of COX-2, whereas COX-1 levels remained unchanged. Despite an increased expression of COX-2 at the protein level, HNPs did not significantly enhance the COX-2 activity, thus the production of the prostaglandin PGI sub(2). HNPs significantly induced the release of endothelin-1 (ET-1) as well as the formation of nitrotyrosine. The HNP-induced COX-2 and ET-1 production was attenuated by the treatment with the oxygen free radical scavenger N-acetyl-L-cysteine and the inhibitors of p38 MAPK and NF- Kappa B, respectively. The angiontensin II pathway did not seem to be involved in the HNP-induced upregulation of COX-2 and ET-1 since the use of the angiotensin-converting enzyme inhibitor enalapril had no effect in this context. In conclusion, HNP may play an important role in the pathogenesis of inflammatory cardiovascular diseases by activating endothelial cells to produce vasoactive by-products as a result of oxidative stress.
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